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Induction of anti‐β 2 ‐glycoprotein I autoantibodies in mice by protein H of Streptococcus pyogenes
Author(s) -
VAN OS G. M. A.,
MEIJERS J. C. M.,
AGAR Ç.,
SERON M. V.,
MARQUART J. A.,
ÅKESSON P.,
URBANUS R. T.,
DERKSEN R. H. W. M.,
HERWALD H.,
MÖRGELIN M.,
DE GROOT P. G.
Publication year - 2011
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2011.04532.x
Subject(s) - streptococcus pyogenes , autoantibody , epitope , glycoprotein , antibody , conformational epitope , chemistry , biology , microbiology and biotechnology , immunology , bacteria , staphylococcus aureus , genetics
Summary. Background: The antiphospholipid syndrome (APS) is characterized by the persistent presence of anti‐β 2 ‐glycoprotein I (β 2 ‐GPI) autoantibodies. β 2 ‐GPI can exist in two conformations. In plasma it is a circular protein, whereas it adopts a fish‐hook conformation after binding to phospholipids. Only the latter conformation is recognized by patient antibodies. β 2 ‐GPI has been shown to interact with Streptococcus pyogenes. Objective: To evaluate the potential of S. pyogenes ‐derived proteins to induce anti‐β 2 ‐GPI autoantibodies. Methods and results: Four S. pyogenes surface proteins (M1 protein, protein H, streptococcal collagen‐like protein A [SclA], and streptococcal collagen‐like protein B [SclB]) were found to interact with β 2 ‐GPI. Only binding to protein H induces a conformational change in β 2 ‐GPI, thereby exposing a cryptic epitope for APS‐related autoantibodies. Mice were injected with the four proteins. Only mice injected with protein H developed antibodies against the patient antibody‐related epitope in domain I of β 2 ‐GPI. Patients with pharyngotonsillitis caused b y S. pyogenes who developed anti‐protein H antibodies also generated anti‐β 2 ‐GPI antibodies. Conclusions: Our study has demonstrated that a bacterial protein can induce a conformational change in β 2 ‐GPI, resulting in the formation of antiβ 2 ‐GPI autoantibodies. This constitutes a novel mechanism for the formation of anti‐β 2 ‐GPI autoantibodies.